This quantity includes a diversity of issues akin to the activation and manipulation of pyrroles, the synthesis of annelated pyrroles utilizing acylation reactions and the synthesis of kainoids, a relations of hugely biologically energetic nitrogen heterocycles.

C h e m i c a l Properties In the following Sections the chemical properties of biguanide and its derivatives are systematically considered. Attention may be drawn to the particularly extensive and detailed recent studies concerning biguanides 412 The Chemistry of Biguanides as sources of guanamines and pyrimidines (Section H). The basic nature and properties of biguanides have already been dealt with in Section VI B. A. Thermal Decomposition 1. Arylbiguanides The thermal decomposition of phenylbiguanide, both in the presence and absence of ammonium chloride and aniline hydrochloride, has been studied in some detail (669) with the following results (equations 1 and 2, R ----Ph) : R _ N H .

The reaction has been extended to 1,1disubstituted biguanides (548) and to several other examples (767, 527). 419 F. Kurzer and E. D. Pitchfork H . Condensation w i t h Esters The reaction of biguanides with esters was first studied in detail by Rackmann (578) who showed that ethyl formate and arylbiguanides gave 2,4-diamino-6-substituted s-triazines (LXXXIII, where R', R" and R" may vary widely). ~NIII q- AlkOH +HgO NHR' (LXXXm} 1. Saturated Esters In 1940, phenylbiguanide and ethyl formate were reported (735) to react at room temperature to give a triazine, also formed on fusion of phenylbiguanide and diphenylformamide at 145 ~ Further experience gained with Paludfine (t55)showed that the products were N~-arylguanamines (LXXXII[; R ' = P h , R ' : R m = H ; or R'=p-C1C~H4; R*=Pr~; R " ~ H).

In the presence of too high a concentration of acid, however, amidinoureas will result (572, 730). Thus, the appropriate reactants give the desired 1-arylbiguanides in boiling 12% hydrochloric acid, but yield N-amidino-N'arylureas in 22% acid. Since 22% hydrochloric acid converts the biguanide into the amidinourea (730), support is provided for the primary formation of the biguanides. NH2 II n 0 NFI A r N H 2 + HsN" C. N H . CN 22% HCI Zl NH ""~0/-"* A r N H 9C- N H . C. N H s II Ii NH NH Time, as well as acid concentration, is a factor controlling the nature of the product.